Herpes Part II Flashcards
Herpes Simplex Type 1
Primary Infection
The primary infection is often subclinical. Some infants get moderate or even severe stomatitis with vesicles throughout the mouth. Incubation period is 1-2 weeks.
Other sites of primary infection include the
nose, eyes, fingers, etc. Virions produced at the site of initial infection infect the sensory nerves there and the infection (probably in the form of nucleocapsids) ascends the nerve to establish a latent infection in the sensory ganglion that corresponds to the initial site.
The latent virus has been isolated from sensory ganglia.
Herpes Simplex Type 1
Recurrent Infection
A recurrent infection begins when extensive viral multiplication is “turned on” in the nucleus of a sensory ganglion cell. The resulting virions are transported down the axon to the cutaneous site corresponding to the primary infection. Here a local infection with vesicular lesions (the cold sores) result. Cold sores are selflimiting local lesions. Circulating antibody is already present as a result of the primary infection and prevents disseminated infection. The cold sore produces many infectious virions. Remember that small amounts of infectious virus are sporadically released without production of lesions.
Herpes Simplex Type 1
Latency
Latent infections can be activated to produce cold
sores by fever, UV light, emotion.
Herpes Simplex Type 2
Primary Infection
Herpes simplex type 2 causes an STD with lesions
on the genitalia. Thus seroconversion is
seen in populations after the age of puberty.
Currently about 20% of the US population is seropositive and thus latently infected. Primary infections may be severe with multiple bilateral lesions but many are asymptomatic. Incubation
period is 1-2 weeks. The primary infection results
in a latent infection of the sensory ganglia cells that innervate the genitalia (sacral ganglia). Recurrent disease has fewer lesions, that are generally unilateral. Chemotherapy with acyclovir is useful to prevent recurrent disease. Most latently infected persons sporadically produce small amounts of infectious virus even though they have no overt lesions.
Herpes Simplex Type 2
Systemic Disease
Virions released into vaginal secretions by
symptomatic (with lesions) or asymptomatic
pregnant women may cause a perinatal infection.
The resulting systemic disease, appearing about 6 days after birth is often fatal (Neonatal herpes simplex).
Most organs are invaded by the virus in the neonatal disease but destruction of liver and adrenals are marked (hepato adrenal necrosis)
Herpes Simplex Type 2
Perinatal Infections
Perinatal infections can occur when the mother is latently infected and has recurrent vaginal lesions at the time of delivery or is without lesion (asymptomatic virus production) at the time of delivery. Perinatal infections can also occur when the mother is acutely infected shortly before delivery. Acute primary infections, particularly those in which the mother has not yet seroconverted at the time of delivery, have the highest likelihood of perinatal infection and of fatal outcome.
Vaginal lesions present before delivery are a strong indication of caesarian section
Herpes Simplex Virus Epidemiology
- HSV-1 > 80% seroprevalence in adults, HSV-2 > 20%
- Spread by (very close contact)
- Cold sores ocular infections, genital sores and encephalitis
- Reactivation and shedding can be with or without overt symptoms
- Excellent nucleoside analog drugs exist, but latency is refractory to therapy
- Vaccination thus far is unsuccessful to HSV
Herpes Simplex Encephalitis
Herpes simplex (mostly type 1) is the most common cause of sporadic (non-epidemic) encephalitis. It is seen as both a primary infection and in patients with a history of recurrent lesions. The route to the CNS is probably neural.
Herpes Simplex Encephalitis
Commonly affected area
The temporal lobe is most commonly infected
and may give rise to temporal lobe symptoms
(auditory or olfactory hallucinations).
Diagnosis of Herpes Simplex Encephalitis
Reliable diagnosis formerly required virus demonstration in biopsy specimen. In most medical
centers this invasive procedure has been replaced
with PCR detection of herpes simplex DNA in the CSF. Rapid diagnosis is important because chemotherapy is available (acyclovir).
An alternative to making a specific laboratory diagnosis is to treat with acyclovir on clinical suspicion of herpes simplex encephalitis.
Herpes Simplex Keratitis
Keratoconjunctivitis
When herpes simplex infects the eye it can lead
to keratitis with the conjuctiva and eyelids affected
as well as the cornea. It typically presents as a unilateral “red eye” with a variable degree of pain or ocular irritation. This is often associated with photophobia. The disease can spread to deeper levels of the eye and cause permanent damage. Patients with recurrent herpes simplex keratitis are at risk of blindness from corneal damage. Treatment is with topical trifluridine or systemic acyclovir
Varicella-Zoster Virus
The primary infection is chickenpox.
Winter-spring epidemics in children are seen every
few years.
Varicella-Zoster Virus
Infection
Infection is by way of the respiratory tract with subsequent viremia. Incubation period two to three weeks; then fever and rash. The lesions of chicken pox are small, itchy vesicles. Characteristically the lesions are in different states of development in the same area of skin.
The infection is probably spread from person to person primarily by viruses shed from the skin lesions. Virus-containing vesicles in the mucosa rupture shortly after they form and shed virus from the respiratory tract which may also spread the infection.
Varicella-Zoster Virus
Immune Deficiency
Patients with an impaired immune response (lymphoma, congenital defect in immunity, chemotherapy for tumors, AIDS, etc., etc.) get a severe and often fatal chickenpox on primary infection. If exposed to the virus they can be passively immunized with IgG from donors known to have high titers of neutralizing antibody
(Varicella-Zoster Immune Globulin: VZIG).
VZIG is less used now because a vaccine is available and because chemotherapy and chemprophylaxsis with acyclovir works well.
CONGENITAL VARICELLA SYNDROME
There is a low (0.5 – 2%) incidence of fetal infection
when a pregnant mother is infected during the first or early second trimester. This is referred to as CONGENITAL VARICELLA SYNDROME, and is characterized by limb atrophy and scarring of the skin on the affected limb. This is much less common than congenital infection with cytomegalovirus
Varicella-Zoster Virus
Latent Infection / Shingles
Latent infections with varicella-zoster virus are established in sensory ganglia (the same as with herpes simplex).
When this latent infection is reactivated virions
move down the axons to the skin. At the cutaneous
site, viral growth produces vesicular lesions that have a unilateral, dermatomal distribution. This is the disease called ZOSTER or SHINGLES.
Zoster may begin with dermatomally distributed
pain before the lesions appear. After recovery
from zoster (lesions healed) some patients have severe local pain in a syndrome called “post-herpetic neuralgia”.
This adverse outcome increases with the age
at which the zoster attack takes place. Acyclovir given in the first 1-2 days can reduce the risk of post-herpetic neuralgia.
Zoster is characterized by monocyte infiltration of the involved ganglion and pain that may precede the cutaneous lesions.
DISSEMINATED ZOSTER
All patients who get zoster are already seropositive as a result of their original chicken pox. This antibody usually prevents viremic spread and results in the dermatomal distribution. Immunosuppressed patients have a higher incidence of zoster and are at risk for
DISSEMINATED ZOSTER in which the virus is spread by viremia and produces lesions beyond the original dermatome. This disseminated disease can be treated with acyclovir
Zoster
At risk Population
All ages are affected but the attack frequency increases with age after 50. This increase in age specific attack rate is probably the result of an aggregated decline in cell-mediated immunity. Other conditions that reduce cell-mediated immunity (AIDS, some anti-cancer drugs, and immunosuppressive drugs) also result in a higher incidence of zoster.
Zoster
Survival
The zoster vesicles contain virus and a case of zoster may be the source of a chickenpox epidemic. Note again the survival of varicella-zoster virus in small populations. Patients recovered from zoster have very high antiviral Ab titers.
